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. 2022 Jan 11;145(2):97-106.
doi: 10.1161/CIRCULATIONAHA.121.056878. Epub 2021 Nov 8.

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

Neel M Butala  1   2 , Kamil F Faridi  3 , Hector Tamez  1 , Jordan B Strom  1 , Yang Song  1 , Changyu Shen  1   4 , Eric A Secemsky  1 , Laura Mauri  5 , Dean J Kereiakes  6 , Jeptha P Curtis  3 , C Michael Gibson  1   7 , Robert W Yeh  1   7
Affiliations

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study

Neel M Butala et al. Circulation. .

Abstract

Background: Differences in patient characteristics, changes in treatment algorithms, and advances in medical technology could each influence the applicability of older randomized trial results to contemporary clinical practice. The DAPT Study (Dual Antiplatelet Therapy) found that longer-duration DAPT decreased ischemic events at the expense of greater bleeding, but subsequent evolution in stent technology and clinical practice may attenuate the benefit of prolonged DAPT in a contemporary population. We evaluated whether the DAPT Study population is different from a contemporary population of US patients receiving percutaneous coronary intervention and estimated the treatment effect of extended-duration antiplatelet therapy after percutaneous coronary intervention in this more contemporary cohort.

Methods: We compared the characteristics of drug-eluting stent-treated patients randomly assigned in the DAPT Study to a sample of more contemporary drug-eluting stent-treated patients in the National Cardiovascular Data Registry CathPCI Registry from July 2016 to June 2017. After linking trial and registry data, we used inverse-odds of trial participation weighting to account for patient and procedural characteristics and estimated a contemporary real-world treatment effect of 30 versus 12 months of DAPT after coronary stent procedures.

Results: The US drug-eluting stent-treated trial cohort included 8864 DAPT Study patients, and the registry cohort included 568 540 patients. Compared with the trial population, registry patients had more comorbidities and were more likely to present with myocardial infarction and receive 2nd-generation drug-eluting stents. After reweighting trial results to represent the registry population, there was no longer a significant effect of prolonged DAPT on reducing stent thrombosis (reweighted treatment effect: -0.40 [95% CI, -0.99% to 0.15%]), major adverse cardiac and cerebrovascular events (reweighted treatment effect, -0.52 [95% CI, -2.62% to 1.03%]), or myocardial infarction (reweighted treatment effect, -0.97% [95% CI, -2.75% to 0.18%]), but the increase in bleeding with prolonged DAPT persisted (reweighted treatment effect, 2.42% [95% CI, 0.79% to 3.91%]).

Conclusions: The differences between the patients and devices used in contemporary clinical practice compared with the DAPT Study were associated with the attenuation of benefits and greater harms attributable to prolonged DAPT duration. These findings limit the applicability of the average treatment effects from the DAPT Study in modern clinical practice.

Keywords: percutaneous coronary intervention; platelet aggregation inhibitors; pragmatic clinical trials as topic.

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Figures

Figure 1.
Figure 1.. Estimating real-world treatment effects of the DAPT Study
Estimating real-world treatment effects of the DAPT Study. The DAPT Study population was reweighted to resemble the contemporary real-world population of patients undergoing PCI with regards to all measured covariates. The DAPT Study randomized treatment effects were then re-estimated in this reweighted sample. The re-weighted trial results represent the cumulative incidence of outcomes expected among patients in the real-world cohort if they had been assigned randomized treatment in the trial and treated according to contemporary standards with regards to stent generation.
Figure 2.
Figure 2.. Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics
Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics. a. stent thrombosis, b. major adverse cardiac and cerebrovascular events, c. GUSTO Moderate or Severe Bleeding, d. BARC 2, 3, or 5 Bleeding
Figure 2.
Figure 2.. Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics
Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics. a. stent thrombosis, b. major adverse cardiac and cerebrovascular events, c. GUSTO Moderate or Severe Bleeding, d. BARC 2, 3, or 5 Bleeding
Figure 2.
Figure 2.. Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics
Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics. a. stent thrombosis, b. major adverse cardiac and cerebrovascular events, c. GUSTO Moderate or Severe Bleeding, d. BARC 2, 3, or 5 Bleeding
Figure 2.
Figure 2.. Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics
Cumulative incidence rate in outcomes for prolonged DAPT versus normal DAPT in trial cohort and reweighted trial cohort to reflect contemporary registry cohort characteristics. a. stent thrombosis, b. major adverse cardiac and cerebrovascular events, c. GUSTO Moderate or Severe Bleeding, d. BARC 2, 3, or 5 Bleeding
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